Responses of intestinal virome to silver nanoparticles: safety assessment by classical virology, whole-genome sequencing and bioinformatics approaches

Kuppan Gokulan,1,* Aschalew Z Bekele,1,* Kenneth L Drake,2 Sangeeta Khare1 1Division of Microbiology, US Food and Drug Administration, National Center for Toxicological Research, Jefferson, AR, USA; 2Seralogix, Inc., Austin, TX, USA *These authors contributed equally to this work Background: Effe...

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Autores principales:	Gokulan K, Bekele AZ, Drake KL, Khare S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Intestinal content Microbiome Phages Silver Nanoparticles Virome Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/495af760fd24446b8a3ee25ec48e8366
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spelling	oai:doaj.org-article:495af760fd24446b8a3ee25ec48e83662021-12-02T03:16:05ZResponses of intestinal virome to silver nanoparticles: safety assessment by classical virology, whole-genome sequencing and bioinformatics approaches1178-2013https://doaj.org/article/495af760fd24446b8a3ee25ec48e83662018-05-01T00:00:00Zhttps://www.dovepress.com/responses-of-intestinal-virome-to-silver-nanoparticles-safety-assessme-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Kuppan Gokulan,1,* Aschalew Z Bekele,1,* Kenneth L Drake,2 Sangeeta Khare1 1Division of Microbiology, US Food and Drug Administration, National Center for Toxicological Research, Jefferson, AR, USA; 2Seralogix, Inc., Austin, TX, USA *These authors contributed equally to this work Background: Effects of silver nanoparticles (AgNP) on the intestinal virome/phage community are mostly unknown. The working hypothesis of this study was that the exposure of pharmaceutical/nanomedicine and other consumer-use material containing silver ions and nanoparticles to the gastrointestinal tract may result in disturbance of the beneficial gut viruses/phages. Methods: This study assesses the impact of AgNP on the survival of individual bacteriophages using classical virology cultivation and electron microscopic techniques. Moreover, how the ingested AgNP may affect the intestinal virus/phages was investigated by conducting whole-genome sequencing (WGS). Results: The viral cultivation methods showed minimal effect on selected viruses during short-term exposure (24 h) to 10 nm AgNP. However, long-term exposure (7 days) resulted in significant reduction in the viral/phage population. Data obtained from WGS were filtered and compared with a nonredundant viral database composed of the complete viral genomes from NCBI using KRAKEN (confidence scoring threshold of 0.5). To compare the relative differential changes, the sequence counts in each treatment group were normalized to account for differences in DNA sequencing library sizes. Bioinformatics techniques were developed to visualize the virome comparative changes in a phylogenic tree graph. The computed data revealed that AgNP had an impact on several intestinal bacteriophages that prey on bacterial genus Enterobacteria, Yersinia and Staphylococcus as host species. Moreover, there was an independent effect of nanoparticles and released ions. Conclusion: Overall, this study reveals that the small-size AgNP could lead to perturbations of the gut microbial ecosystem, leading to the inactivation of resident phages that play an important role in influencing gastrointestinal health. Keywords: bacteriophages, intestine, microbiome, nanoparticle, virome, WGS, intestinal content, silver nanoparticlesGokulan KBekele AZDrake KLKhare SDove Medical PressarticleIntestinal contentMicrobiomePhagesSilver NanoparticlesViromeMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 2857-2867 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Intestinal content Microbiome Phages Silver Nanoparticles Virome Medicine (General) R5-920
spellingShingle	Intestinal content Microbiome Phages Silver Nanoparticles Virome Medicine (General) R5-920 Gokulan K Bekele AZ Drake KL Khare S Responses of intestinal virome to silver nanoparticles: safety assessment by classical virology, whole-genome sequencing and bioinformatics approaches
description	Kuppan Gokulan,1,* Aschalew Z Bekele,1,* Kenneth L Drake,2 Sangeeta Khare1 1Division of Microbiology, US Food and Drug Administration, National Center for Toxicological Research, Jefferson, AR, USA; 2Seralogix, Inc., Austin, TX, USA *These authors contributed equally to this work Background: Effects of silver nanoparticles (AgNP) on the intestinal virome/phage community are mostly unknown. The working hypothesis of this study was that the exposure of pharmaceutical/nanomedicine and other consumer-use material containing silver ions and nanoparticles to the gastrointestinal tract may result in disturbance of the beneficial gut viruses/phages. Methods: This study assesses the impact of AgNP on the survival of individual bacteriophages using classical virology cultivation and electron microscopic techniques. Moreover, how the ingested AgNP may affect the intestinal virus/phages was investigated by conducting whole-genome sequencing (WGS). Results: The viral cultivation methods showed minimal effect on selected viruses during short-term exposure (24 h) to 10 nm AgNP. However, long-term exposure (7 days) resulted in significant reduction in the viral/phage population. Data obtained from WGS were filtered and compared with a nonredundant viral database composed of the complete viral genomes from NCBI using KRAKEN (confidence scoring threshold of 0.5). To compare the relative differential changes, the sequence counts in each treatment group were normalized to account for differences in DNA sequencing library sizes. Bioinformatics techniques were developed to visualize the virome comparative changes in a phylogenic tree graph. The computed data revealed that AgNP had an impact on several intestinal bacteriophages that prey on bacterial genus Enterobacteria, Yersinia and Staphylococcus as host species. Moreover, there was an independent effect of nanoparticles and released ions. Conclusion: Overall, this study reveals that the small-size AgNP could lead to perturbations of the gut microbial ecosystem, leading to the inactivation of resident phages that play an important role in influencing gastrointestinal health. Keywords: bacteriophages, intestine, microbiome, nanoparticle, virome, WGS, intestinal content, silver nanoparticles
format	article
author	Gokulan K Bekele AZ Drake KL Khare S
author_facet	Gokulan K Bekele AZ Drake KL Khare S
author_sort	Gokulan K
title	Responses of intestinal virome to silver nanoparticles: safety assessment by classical virology, whole-genome sequencing and bioinformatics approaches
title_short	Responses of intestinal virome to silver nanoparticles: safety assessment by classical virology, whole-genome sequencing and bioinformatics approaches
title_full	Responses of intestinal virome to silver nanoparticles: safety assessment by classical virology, whole-genome sequencing and bioinformatics approaches
title_fullStr	Responses of intestinal virome to silver nanoparticles: safety assessment by classical virology, whole-genome sequencing and bioinformatics approaches
title_full_unstemmed	Responses of intestinal virome to silver nanoparticles: safety assessment by classical virology, whole-genome sequencing and bioinformatics approaches
title_sort	responses of intestinal virome to silver nanoparticles: safety assessment by classical virology, whole-genome sequencing and bioinformatics approaches
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/495af760fd24446b8a3ee25ec48e8366
work_keys_str_mv	AT gokulank responsesofintestinalvirometosilvernanoparticlessafetyassessmentbyclassicalvirologywholegenomesequencingandbioinformaticsapproaches AT bekeleaz responsesofintestinalvirometosilvernanoparticlessafetyassessmentbyclassicalvirologywholegenomesequencingandbioinformaticsapproaches AT drakekl responsesofintestinalvirometosilvernanoparticlessafetyassessmentbyclassicalvirologywholegenomesequencingandbioinformaticsapproaches AT khares responsesofintestinalvirometosilvernanoparticlessafetyassessmentbyclassicalvirologywholegenomesequencingandbioinformaticsapproaches
_version_	1718401850199244800

Responses of intestinal virome to silver nanoparticles: safety assessment by classical virology, whole-genome sequencing and bioinformatics approaches

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